The respiratory muscles are a major determinant of thoracic cavity shape and; therefore, of the regional ventilation distribution. Respiratory insufficiency is the cause of death in many primary neuromuscular disorders. Furthermore, respiratory muscle fatigue is believed to be the proximate cause of hypercarbic respiratory failure, which causes the death of many patients with chronic lung disease, yet the micromechanics of the respiratory muscles are very poorly understood. An understanding of the micromechanics of the diaphragm, the primary respiratory muscle, is fundamental to any explanation of its physiological or pathological behavior. The diaphragm has a morphologically composite structure that dictates its macromechanical behavior under physiological loads. The diaphragm, unlike other skeletal muscles is under biaxial load. Therefore, the mechanism of force transmissions between the fibers and connective tissue is more complex. our overriding hypothesis is that the macromechanics of the major respiratory muscle, the diaphragm, are mainly determined by the shape and surface area of the fibers, connective tissue and muscle-tendon junctions (MTJ), as well as by the fiber architectural arrangement. We hypothesize that the costal diaphragm has an in-series fiber architecture, and tension is transmitted between muscle fibers along their lateral surfaces through the connective tissue. We also hypothesize that the degree of amplification of the membrane area across where force is transmitted during biaxial loading of the diaphragm is greater than that would occur if the MTJ were the sole site of tension transmission. We further hypothesize that the stiffness near the MTJ in the direction transverse the long axis of the fibers is greater than stiffness along the fibers. This may be due to an increase of the proportion of connective tissue to muscle fibers near the MTJ. Furthermore, we hypothesize that the stress concentration of fiber-ends is such that stress concentrations at the end of a fiber are determined mainly by the change in the shape of fiber-ends due to a biaxially loaded fiber-connective tissue composite. Our objectives are to relate the micromechanics of the diaphragm to its macromechanical behavior by determining the effect of biaxial loading on the cross-sectional shape and area of the muscle fibers, the structure of connective tissue, and MTJ; determine the tension among muscle fibers and across the MTJ; and finally, model micromechanics of the fiber-connective tissue composite and the MTJ structure using well established computational methods for finite element modeling and analysis; in particular, we will determine the tension distribution within the fibers and the connective tissue as well as their interface due to biaxial loads. This award will directly facilitate the applicant's integration of new techniques in micromechanics to complement his established capabilities in bioengineering, biomathematics and macromechanics of the diaphragm.